Raman investigation of the charge-density-wave mixed-crystal system 1T-TaS\u3csub\u3e2-x\u3c/sub\u3eSe\u3csub\u3ex\u3c/sub\u3e

The results of Raman scattering measurements on the mixed-crystal system 1T- TaS2-xSex in the commensurate charge-density-wave state are reported. In the pure compounds, our measurements indicate that a strong LA-TA phonon interaction at the distortion wave-vector results in additional coupled charge-density-wave-lattice excitations. These excitations can be followed over the whole range of concentrations in the mixed crystals. The concentration dependences of the mode frequencies are treated using an effective oscillator model

Raman investigation of the charge-density-wave mixed-crystal system 1T-TaS\u3csub\u3e2-x\u3c/sub\u3eSe\u3csub\u3ex\u3c/sub\u3e

The results of Raman scattering measurements on the mixed-crystal system 1T- TaS2-xSex in the commensurate charge-density-wave state are reported. In the pure compounds, our measurements indicate that a strong LA-TA phonon interaction at the distortion wave-vector results in additional coupled charge-density-wave-lattice excitations. These excitations can be followed over the whole range of concentrations in the mixed crystals. The concentration dependences of the mode frequencies are treated using an effective oscillator model

TDP43 proteinopathy is associated with aberrant DNA methylation in human amyotrophic lateral sclerosis

Background Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by motor neurone (MN) degeneration and death. ALS can be sporadic (sALS) or familial, with a number of associated gene mutations, including C9orf72 (C9ALS). DNA methylation is an epigenetic mechanism whereby a methyl group is attached to a cytosine (5mC), resulting in gene expression repression. 5mC can be further oxidized to 5‐hydroxymethylcytosine (5hmC). DNA methylation has been studied in other neurodegenerative diseases, but little work has been conducted in ALS. Aims To assess differences in DNA methylation in individuals with ALS and the relationship between DNA methylation and TDP43 pathology. Methods Post mortem tissue from controls, sALS cases and C9ALS cases were assessed by immunohistochemistry for 5mC and 5hmC in spinal cord, motor cortex and prefrontal cortex. LMNs were extracted from a subset of cases using laser capture microdissection. DNA from these underwent analysis using the MethylationEPIC array to determine which molecular processes were most affected. Results There were higher levels of 5mC and 5hmC in sALS and C9ALS in the residual lower motor neurones (LMNs) of the spinal cord. Importantly, in LMNs with TDP43 pathology there was less nuclear 5mC and 5hmC compared to the majority of residual LMNs that lacked TDP43 pathology. Enrichment analysis of the array data suggested RNA metabolism was particularly affected. Conclusions DNA methylation is a contributory factor in ALS LMN pathology. This is not so for glia or neocortical neurones

System responses to Holocene relative sea-level rise and sediment supply in a macrotidal estuary

Estuaries are at the interface of marine and terrestrial systems and as such, are subject to environmental change arising from multiple driving mechanisms, with the interplay between the dominant controls varying spatially and temporally. Relative sea-level (RSL) change and sediment supply can play a significant role in driving environmental change. This study examines the relative influence of these drivers during the Holocene. Biostratigraphic records and RSL data are presented from two locations in the inner portion and upper reaches of the macrotidal Humber Estuary, eastern England. The results provide a new terrestrial limiting point and six sea-level index points, two of which at c. 1500 cal years BP provide the youngest sea-level index points for the inner estuary. An early-mid Holocene tidal lagoon system, that lacks modern equivalent, is recorded at one site. The results indicate a shift in the dominance of RSL rise driving the early Holocene creation of wetlands, to sediment supply dominating changes in the mid-late Holocene against the backdrop of a reduced rate of RSL rise, with a submergence of wetlands evident after c. 4000 cal years BP. The persistence of fen carr evident between c. 6800 and 5500 cal years BP suggests stability and resilience of the peatland system to continuing RSL rise. As rates of contemporary RSL rise increase, combined with climate and human impacts on the landscape, the drivers of change in these type of estuary systems will shift, with the records providing analogues of potential system responses that can help inform coastal management strategies

The UK HeartSpare study: randomised evaluation of voluntary deep-inspiratory breath-hold in women undergoing breast radiotherapy

Purpose: to determine whether voluntary deep-inspiratory breath-hold (v_DIBH) and deep-inspiratory breath-hold with the active breathing coordinator™ (ABC_DIBH) in patients undergoing left breast radiotherapy are comparable in terms of normal-tissue sparing, positional reproducibility and feasibility of delivery.Methods: following surgery for early breast cancer, patients underwent planning-CT scans in v_DIBH and ABC_DIBH. Patients were randomised to receive one technique for fractions 1–7 and the second technique for fractions 8–15 (40?Gy/15 fractions total). Daily electronic portal imaging (EPI) was performed and matched to digitally-reconstructed radiographs. Cone-beam CT (CBCT) images were acquired for 6/15 fractions and matched to planning-CT data. Population systematic (?) and random errors (?) were estimated. Heart, left-anterior-descending coronary artery, and lung doses were calculated. Patient comfort, radiographer satisfaction and scanning/treatment times were recorded. Within-patient comparisons between the two techniques used the paired t-test or Wilcoxon signed-rank test.Results: twenty-three patients were recruited. All completed treatment with both techniques. EPI-derived ? were ?1.8?mm (v_DIBH) and ?2.0?mm (ABC_DIBH) and ? ?2.5?mm (v_DIBH) and ?2.2?mm (ABC_DIBH) (all p non-significant). CBCT-derived ? were ?3.9?mm (v_DIBH) and ?4.9?mm (ABC_DIBH) and ? ??4.1?mm (v_DIBH) and ??3.8?mm (ABC_DIBH). There was no significant difference between techniques in terms of normal-tissue doses (all p non-significant). Patients and radiographers preferred v_DIBH (p?=?0.007, p?=?0.03, respectively). Scanning/treatment setup times were shorter for v_DIBH (p?=?0.02, p?=?0.04, respectively).Conclusions: v_DIBH and ABC_DIBH are comparable in terms of positional reproducibility and normal tissue sparing. v_DIBH is preferred by patients and radiographers, takes less time to deliver, and is cheaper than ABC_DIB

Axonal Preservation in Deep Subcortical White Matter Lesions in the Ageing Brain

Cerebral white matters lesions (WML) are seen in 94% of the population aged 64 and over and are associated with cognitive decline and depression. We used immunohistochemistry and stereological methods on post mortem brain samples derived from the Medical Research Council Cognitive Function and Ageing Study (MRC-CFAS) cohort to investigate the axonal density within deep subcortical lesions. There was no significant difference between the lesional and control white matter, therefore, we conclude that there is axonal preservation within these lesions that are characterized by demyelination

THSim v3.2: The Talking Heads simulation tool

The field of language evolution and computation may benefit from using efficient and robust simulation tools that are based on widely exploited principles within the field. The tool presented in this paper is one that could fulfil such needs. The paper presents an overview of the tool -- THSim v3.2 -- and discusses some research questions that can be investigated with it

Neuropathological characterisation of a novel TBK1 loss of function mutation associated with amyotrophic lateral sclerosis

Mutations in TANK binding kinase gene (TBK1) have been identified as causative in amyotrophic lateral sclerosis (ALS). Here, we examine the spectrum of TBK1 mutations in a cohort of ALS patients from Northern England, comparing missense and loss of function mutations with clinical phenotype. Analysis of 290 ALS cases identified seven variants, including one novel in-frame deletion (p.Ile85del). In silico analysis and review of the literature suggested that four variants, one nonsense mutation (p.Glu2Ter), two in-frame deletions (p.Ile85del, p.Glu643del) and one missense mutation (p.Gln565Pro) were pathogenic, whilst the remaining three missense mutations were variants of uncertain significance or benign. Post-mortem material was available from the patient with the novel in-frame deletion. Neuropathological examination established this individual had classical ALS pathology, with moderate phosphorylated TDP-43 neuronal and glial cytoplasmic inclusions in the motor cortex, skein-like inclusions in the lower motor neurons and “pre-inclusions” in the medulla. This corresponds to Type B FTLD-TDP pathology and is consistent with previously published literature on TBK1 mutants. In addition to demonstrating no changes in TBK1 staining, we are the first to show there was no differential expression of interferon regulatory factor IRF3, a downstream effector of TBK1 in the innate immunity pathway, in the TBK1-mutant tissue compared to controls. Comparison of clinical and neuropathological data, however, suggests that TBK1-ALS cases show classical ALS pathology but no specific phenotype